Study Questions:

What is the safety and efficacy of edoxaban treatment for cancer-associated venous thromboembolism (VTE)?

Methods:

The authors randomized 1,050 patients with cancer-associated VTE to receive either dalteparin, a low-molecular-weight heparin (LMWH), or edoxaban after a 5-day lead-in period of LMWH. Both groups received anticoagulation for between 6 and 12 months. The primary outcome was a composite of recurrent VTE or major bleeding at 12 months.

Results:

The composite primary endpoint of recurrent VTE or major bleeding occurred in 12.8% of the edoxaban-treated group and 13.5% of the LMWH-treated group (hazard ratio, 0.97; 95% confidence interval [CI], 0.70-1.36; p = 0.006 for noninferiority). Recurrent VTE occurred in 7.9% of the edoxaban-treated patients and 11.3% of the LMWH-treated patients (risk difference, -3.4% points; 95% CI, -7.0 to 0.2). Major bleeding occurred in 6.9% of the edoxaban-treated group and 4.0% of the dalteparin group (risk difference, 2.9% points; 95% CI, 0.1-5.6).

Conclusions:

The authors concluded that edoxaban was noninferior to LMWH for the composite outcome of recurrent VTE and major bleeding among patients with cancer-associated VTE.

Perspective:

In patients with cancer-associated VTE, use of LMWH for 6 months is a grade 2B recommendation given lower rates of recurrent VTE (Chest 2016;149:315-52). This study is the first large, randomized trial comparing LMWH to a direct oral anticoagulant in cancer-associated VTE patients. Interestingly, patients receiving edoxaban have a numerically lower rate of recurrent VTE, but a higher rate of major bleeding. It is possible that this represents better adherence to edoxaban (oral) as compared to LMWH (subcutaneous injection) and/or longer use of edoxaban as compared to LMWH in the study groups (median 211 days vs. 184 days, respectively). How these results will translate to other direct oral anticoagulants (e.g., apixaban and rivaroxaban), especially without the use of a parenteral lead-in treatment period, remains to be studied.